© Springer Science+Business Media Dordrecht 2015Deborah Mascalzoni (ed.)Ethics, Law and Governance of BiobankingThe International Library of Ethics, Law and Technology1410.1007/978-94-017-9573-9_13
A Bold Experiment: Iceland’s Genomic Venture
University of California, Berkeley, USA
In 2008, like an overheated nuclear reactor, Iceland’s banking sector melted down. After investors pulled money out of Iceland en masse, the Icelandic government took control over the last and largest of the country’s three major banks and shut down the stock exchange. On October 9, 2008, the New York Times reported that “Iceland’s financial system collapsed,” with a University of Iceland professor stating for the record that “Iceland is bankrupt… The Icelandic krona is history.” A fact-finding team from the International Monetary Fund had been in Iceland all week and had enacted an emergency financing system, expediting loans to the country (Pfanner 2008). Reykjavik, where two-thirds of Iceland’s 300,000 people live, had been the center of one of the world’s fastest economic booms. It was now the site of one of its greatest crashes. But out of the ashes grew hope: on November 20, 2008, Iceland received international backing in the form of a $2.1 billion loan by the International Monetary Fund and an important guarantee by a group of Scandinavian countries (Jolly 2008).
Like the Icelandic economy, deCODE Genetics Inc.—the progenitor of modern genomic biobanks and a touchstone for other major population genomics initiatives around the world—has emerged from bankruptcy. Built on technological advances in the late 1990s and a bold entrepreneurial vision, the company helped transform medical and genealogical information into a new type of commodity. Their scientific and social innovations—or more precisely, the controversies they have spawned—also helped precipitate the development of global norms governing the relations between citizens, medical information, markets, and the state.
By scientific standards, the company is widely regarded as a success: deCODE has reported many markers for diseases such as diabetes, heart disease, and cancer, and has published widely in top journals such as Nature and Science (Kaiser 2009). However, by the time the Icelandic economy imploded, deCODE Genetics already had long-standing financial problems. The business model proved to be shaky: genetic variants are often quite rare, and account for very little variation, reducing their utility as drug targets or genetic tests. As anthropologist Mike Fortun has argued, deCODE’s value has always been—similar to the biotech industry as a whole—highly speculative and predicated on promises (Fortun 2008).1 Desperate for more immediate revenue streams, the company launched “deCODEme” in November 2007, becoming one of a handful of private companies offering customers a personal view of their genetic code and an analysis of certain traits, diseases markers and drug sensitivities. Like its competitor and predecessor in the personal genomics business, “23andMe” of California, “deCODEme” claims to provide insights into disease variants and geographical origins.
Despite these strategic turns and with mounting liquidity problems, deCODE Genetics filed for bankruptcy on November 17, 2009. But just as the Icelandic banks found financial angels a year previously, so did the company. On January 21, 2010, deCODE emerged from financial limbo when two U.S.-based venture capital companies took over the company. DeCODE stated that would it continue conducting genetics research and gene-based diagnostics, but that it would cease efforts to develop drugs from its discoveries. Earl Collier—an attorney and previously vice president of Genzyme and a member of deCODE’s board of directors—would be its new CEO. The company’s previous CEO and notorious co-founder, Dr. Kari Stefansson, would be the new head of research.
Until the company was acquired, there was wide speculation as to what would happen to the biobank itself. One company official said the company had been “talking to a whole range of present and potential customers and partners from pharma to biotech to government and academic groups” (Fortun 2008). Clearly, deCODE’s biobank had become a “private asset,” but the venture had started as a unique blending of public and private: through an enabling statute and commercial license, deCODE would gain access to national health records for collection, storage and research; in exchange, the country would get a national electronic health record system, and the allure of a biotechnology sector that might retain Icelandic scientists. In the process, the legislation would try to create a new kind of public-private biotech company. DeCODE continues to find genetic factors, and lives on as a commercial enterprise, but this bold public-private experiment was a failure. It remains important to narrate the life and death of Iceland’s so-called National Health Sector Database (HSD) project, for it retains important meanings for large-scale biobanks today.
2 Iceland’s Health Sector Database Act
In December 1998, the Iceland Parliament passed the Act on a Health Sector Database (HSD Act) by a vote of 37–20, with 6 abstentions. The Act set out a new regime for the control of citizen health information in a modern democracy. Such information was at once declared a “national resource” to be controlled by the state, and allocated to private industry for inclusion into a commercial genomic database of national scope. The Act immediately took on international significance and has been written about widely by journalists and scholars alike.
The core of the Health Sector Database Act (HSD Act) was the authorization of the database’s creation and operation in Iceland by the private sector licensee, with a reversion of the computerized health data to the state after the license term.2 The license to operate the database could be granted for a renewable term of no more than 12 years and had to meet the requirements of Iceland’s Data Protection Commission, which had been created by a previously enacted privacy law. DeCODE Genetics secured the license to create and operate the HSD in 2000, but this was a fait accompli from Bill’s earliest days. Notes from the Bill state that the idea for the database initiated with deCODE and Kari Stefansson, and the company reportedly drafted the first version of the bill as early as the summer of 1997.3 DeCODE’s plans to link the health data with genetic and genealogical information were widely known, although the Act itself said nothing about biological samples or DNA, and did not mention genealogical records.
The Act authorized the licensee to use the data for profit, but it provided for the protection of privacy in a number of ways. First, the licensee could not grant direct access to the database or information it contained to third parties. Second, it would have to process the information itself in ways that could not be linked to identifiable individuals. The Act provided that the licensee may be civilly liable for negligent disclosure of information and authorized other penalties, including fines, imprisonment, and possible revocation of the license for violations, by the licensee or others, of the Act, the license, or government regulations under the Act.
The HSD Act’s most controversial provision authorized the transfer of all medical record data to the licensee for commercial development without the express consent of individuals, invoking a rule of “presumed consent.” Further, information of the deceased would be automatically be included, despite the potential privacy interests of relatives and individuals. Icelanders had 6 months after the passage of the act to opt-out of the database unconditionally, a provision that had only been added to the Act after the initial version drew significant criticism for its lack of informed consent. The new version also specified a more rigorous encryption architecture for the health information, and provided for lower fees for non-commercial access to the database.
A small and vocal percentage of Icelandic civil society objected, and strenuously. The Icelandic Medical Association publicly opposed both iterations of the HSD Bill for what it saw as its ethical short comings: the failure to protect the rights of research subjects to have informed consent, the lack of a mechanisms for subjects to withdraw from the database once they are entered in, and the monopolistic aspects of the license.4 Furthermore, a small network of physicians, scientists, human rights activists, intellectuals, and patient activists formed a group in opposition to the HSD ACT called Mannvernd. Mannvernd’s English subtitle was the Association of Icelanders for Ethics in Science and Medicine. The Icelandic word mannvernd means “human protection,” and this captures the organizing idea of the group, namely that the “Health Sector Database Act infringes on human rights, personal privacy, and on accepted medical, scientific and commercial standards.”5
Despite the development of a network of scientists and doctors organized into opposition to the HSD Act, the law was passed as noted above in December 1998. By claiming the authority to transfer to a commercial entity the medical information of all Icelandic citizens, the government imposed a new regime of control of Icelandic medical records. One important legal effect was to sever the ability of doctors to prevent their health institutions from handing over patient medical data without their authorization. The directors of health institutions would be empowered to negotiate all transfer of information, without review by any independent ethics committees, the normal ethical requirement for accessing medical records for research. At the same time, the government claimed the power to provide access to the medical information, and indeed to license it for commercial use: because the state paid for the medical care giving rise to the data, the state may control and “exploit” that data for the benefit of Iceland. Rhetorically, the Act both denies that medical data can be owned, but this language is mere formalism: access, use, and control are nothing but the traditional components of property.6 In effect, the state reduces the complex web of legal interests around the medical data by cutting off the doctors, and asserts the power to license, a property interest (Winickoff 2003).
By December 1998, the critics had been effectively neutralized by the passage of the HSD Act. The path was paved for deCODE’s exclusive commercial access to the trove of medical data on all Icelanders, and the essential conditions for construction of the Health Sector Database had been established. But we have yet to explain how such a political stroke was accomplished.
3 The Birth of the Health Sector Database
The passage of the Health Sector Database Act, was a watershed event as much for the fields of genomic research, venture capital, and bioethics as it was for Icelandic society: in one unprecedented stroke, a national parliament had authorized the transfer of citizen medical information to a private corporation for commercial exploitation and development, and without the a priori permission of individual citizens. Here we explore how such a coup for Stefansson, CEO of deCODE, could only be achieved through the effective enrollment of Iceland’s natural and social history in its business plan.7 With a national heritage in tow, the business narrative would in turn have to persuade American venture capitalists and their scientific advisors, a majority of Icelandic MPs, and the public itself that their interests necessarily lay in the passage of the Health Sector Database Act. The effectiveness of Stefansson’s pitch lay in its versatile ability to address the most pressing problems of these key constituencies.
3.1 Enrolling Iceland’s Natural and Social History
Stefansson’s genomic vision of Iceland was predicated upon a single compelling theory, namely that Iceland was likely to be a very valuable place to hunt for genetic factors of common human diseases. This hypothesis was supported by a set of foundational claims about Iceland’s natural and social history. First and foremost was the idea that Icelanders were a genetically homogeneous people because of their historic isolation. In a 1995 business plan, and in language that would be echoed throughout the debates about the HSD Act, Stefansson wrote,
Iceland is a small island in the North Atlantic which was inhabited between the years 870 and 930 AD, mostly by Norwegian entrepreneurs and Irish slaves. The year 1000 AD [sic], the population was around 70,000 but around the year 1410 AD the Plague had reduced it down to approximately 30,000. The population had again grown to about 70,000 when at 1700 AD Hekla, the most powerful volcano in the history of Europe, spew lava and ash all over Iceland which led to a famine that reduced the population again down to approximately 30,000. Today, the population of Iceland is 270,000 and they are almost all derived from the original settlers or 30,000 of their descendants who lived in the country around the year 1410 AD and another 30,000 who lived in the country around the year 1710 AD. Therefore, the Icelanders are genetically a homogeneous people and they display a strong founder effect; by following genetic markers it is possible to trace a common origin of a large proportion of them (Stefansson 1994).
This was not a simple claim of genetic homogeneity, but one embedded in a colorful natural history of the Icelandic genome replete with plagues, volcanic eruptions, and famines. Stefansson draws a powerful connection between the founder effect8 that helps make Iceland attractive for gene hunting, and the founders themselves. Although the “facts” of Icelandic homogeneity would become contested within the pages of top science journals as the HSD controversy developed,9 the idea of homogeneity played powerfully both inside and outside Iceland.
Second was the existence in Iceland of intricate and detailed genealogical records. In its early business plans, Stefansson touted the existence of a lineage database for 100 % of Icelanders back to 1910 and 85 % of Icelanders back to 1800, and explained how this would make it “relatively easy to determine relationships between participants or subjects in genetics studies done in Iceland.”10 A third foundational claim was the existence of high quality medical records dating back to the beginning of the Icelandic national health service in 1920, many of which were “centralized and accessible.” Hence, the business plan explained, “it is relatively easy to find a match between genotypes of Icelanders and whatever genetic traits are reflected in their diseases or health.”
As Stefansson and company representatives would explain over and over again to Icelanders, foreigners, and investors alike, these factors gave Iceland an advantage for discovering new genetic factors for disease. If all three resources—Icelanders DNA, genealogies, and the phenotypic data—could be linked together, it would create a uniquely powerful tool for conducting genetic linkage studies as well as allelic association studies. This tripartite and integrated database was the technological bore that would locate genetic diamonds in the rough. The scientific logic was simple: with fewer variations in alleles because of genetic homogeneity, it would in theory be easier to identify candidate genetic variations that were associated with disease. And the idea of folding health data, genetic data, and the genealogical information—compiled through generations of Icelanders—into a single resource was as culturally compelling to venture capitalists as it was to Icelanders. It was a powerful symbol of Iceland itself.
3.2 Enrolling Venture Capitalists
The mid-1990s were boom years for venture capital, and biotech investors and their scientific advisors were looking for big ideas that would solve big problems. One of the big scientific and political problems facing genetics in the mid-90s involved how to translate the massive amount of new genetic code being generated by the public human genome projects into discoveries and therapies. Gene hunting was turning out to be harder than anticipated: it proved to be difficult to identify specific genetic variants that caused common diseases, thus shifting the understanding of disease to polygenic and epigenetic models of causation. Some argued that in order to sort out more complex mechanisms, larger populations of people manifesting both health and illness would need to be sequenced, studied, and compared. Taking a “population” approach to genomics would not have been imaginable even a few years previously, as doing such studies at the desired scales required recent advances in DNA sequencing and information technology that gave birth the nascent field of “bioinformatics.”11
What was needed were promising populations of research subjects upon which these new tools could be turned. As Stefansson put it in his business plan, “it is a commonly held view that the next big steps in the genetics of human diseases will be taken by those who have access to the most suitable populations rather than by those who ask questions, or develop new technologies.” Stefansson was correct that major powerhouses of human genetics, both in academia and in industry, were searching for the appropriate populations on which to apply these new tools and that Icelanders would be appealing. A now famous letter to Stefansson dated 26 May 1995, Kevin J. Kinsella, the President and CEO of Sequana Therapeutics and already involved in the gene hunting business,12 adopted Stefansson’s naturalized account of Iceland’s genomic potential:
As we discussed, Iceland is perhaps the ideal genetic laboratory since there has been virtually no immigration, … it is of manageable size (200,000+ inhabitants), is an island expected to have many founder effects, has high quality national healthcare – from which we can expect excellent disease diagnosis, has formidable genealogies and the population is Caucasian – of most interest to pharmaceutical companies.13
Stefansson managed to raise roughly $12 million in U.S. venture capital in an initial round, and on this strength, another $25 million from Icelandic institutional investors.14 In 1996, Red Herring, a prominent U.S. technology business magazine, declared Stefansson one of their “entrepreneurs of the year,” (Rose 2001) and deCODE became a Delaware corporation. Stefansson’s ability to raise this seed money indicates that the biotech venture firms and their scientific advisors were convinced that Iceland’s population was potentially a unique resource for untangling the complex genetic factors of disease, and for addressing the new problems for translation emerging from the American-led human genome project.
Presenting Iceland as a promising solution to the problem of finding a population was perhaps enough to achieve a first round of major venture funding, but that raised another problem that would have to be solved before large institution investors came on board: the problem of enclosure.15 In short, even if the Icelandic population—with its comparative homogeneity, its genealogies, and its health records—presented a promising opportunity to find disease factors when they are all thrown together, how could these common resources be packaged in such a way as to attract investment? What would give deCODE an advantage over some other highly capitalized biotech firm in order to engage in this gene-hunting venture?
Stefansson realized that some sort of exclusive privatization agreement with Iceland’s health ministry and government authorities would an indispensable piece of any business plan—for therein lay deCODE’s particular competitive advantage. Just exactly what that arrangement would look like became clear when the firm reportedly faxed the first draft of the Health Sector Database Act to Iceland’s Ministry of Health in 199716: the authorization of the Icelandic government granting an exclusive licensee the power to create and operate a database containing health record information of all Icelandic citizens for commercial biomedical research and the now famous regime of “presumed consent.” Other companies would have to work through individual informed consent, a much more time consuming process that would yield fewer participants. This ingenious proposal was not a direct act of enclosure, as the medical records in paper form would still be freely available to other researchers. But the Health Sector Database Act amounted to an indirect act of enclosure—a regulatory subsidy that would cost the nation nothing out-of-pocket, yet confer deCODE unique terms of access to a newly imagined commons.
In Fall 1997, the draft of the Bill on a Health Sector Database had not been made public, but Iceland’s Prime Minister, David Oddsson was already publicly declaring his support for deCODE’s plans to build a genotypic-phenotypic-genealogical database, even in the face of traditional ethical restraints (Rose 2001). In February 1998, deCODE struck a deal with Hoffman-LaRoche, then the fourth largest pharmaceutical company in existence, for rights to discoveries derived from their existing work. David Oddsson reportedly “passed the pen” between the two companies for their meeting in Reykjavik. This deal was worth a reported $200 million in benchmark payments over 5 years, and gave deCODE and Stefansson national celebrity status and global recognition.17 But it remained to convince the Icelandic Parliament, and the Icelandic public, that granting access and use rights to deCODE on an exclusive and “presumed consent” basis was a good idea. As we will see, enrolling U.S. venture capital and global pharmaceutical giants went a long way towards this challenge.
3.3 Enrolling Politicians and the Public
Commentaries regarding the passage of the HSD Act have espoused different theories as to why the majority Independence Party carried it through the Althing, and why the Iceland people seemed to go along. DeCODE was better able to control the public discourse through a US-style publicity campaign in which critics were out-muscled and out-maneuvered, and passage reflected the confluence of strong lobbying by deCODE, a strong parliamentary majority, and party discipline.18 But to read the passage of the Act merely as a case of special interest politics would miss something crucial. Specifically, it would miss the important ways in which deCODE’s rhetoric addressed the central political problem of Iceland as it looked towards the 21st century. This was the pressing problem of survival itself: how could such a remote island society best leverage its natural and social resources in order to remain a viable sovereign nation in the global order?
Icelandic society has sought independence throughout its long history. Whether it has been the Norwegian or Danish monarchy, raiding Vikings, or the modern behemoths of the European Union and the United States, Iceland has struggled with foreign political determination.19 The HSD Act passed because deCODE’s theory spoke boldly to the nation’s deepest aspirations and fears about survival and independence in the global economy. For some years, fishing has provided 70 % of export earnings and employed 4 % of the work force and the Icelandic economy remains vulnerable to declining fish stocks as well as to fluctuations in world prices for its major exports: fish and fish products, aluminum, and ferrosilicon. But since the mid-1990s, Iceland had started a concerted campaign to develop new economic sectors such as information technology, financial services, and tourism. Biotechnology was emblematic of the sort of knowledge-based industry that Iceland’s Independence Party viewed as a solution, and deCODE was poised to launch this sector. And for its part, the Progressive Party in Iceland, which controlled the Health ministry and was part of the majority coalition, was more than willing to be led by this vision, perhaps convinced that this was a cheap way to computerize Iceland’s health system.
Politicians could also make the argument that helping build a strong deCODE would stem the tide of brain drain that many feared was weakening the island nation. Stefansson had created his commercial laboratory near Reykjavík by November 1997 to be operated under deCODE’s Iceland subsidiary, Íslensk Erfðagreining (IE), and in a short amount of time the company had spent more on research than the Icelandic Government’s entire annual research budget, roughly $65 million. The consequences of “brain drain” are not only economic, of course, but also social: families find themselves pulled apart. The idea of the tri-partite genomic database—weaving together as it does individuals and families, past and present, into a single entity—presented a potent symbol of collective strength. The theme of solidarity, through the idea that deCODE could help keep families together, was invoked to outweigh abstract notions about the autonomy, patient-doctor confidentiality, and the erosion of scientific integrity.
The HSD Act’s critics had trouble effectively countering the economic, political and cultural strength of the deCODE-Independence Party alliance. Pétur Hauksson, a psychiatrist and human rights advocate, led Mannvernd in its efforts to criticize the project in the public sphere when the Icelandic Minister of Health, Ingibjörg Pálmadóttir introduced the first version of the Bill to the Althing. For Hauksson, the Bill was illegal both under Iceland’s right to privacy20 as well as under the Helsinki Declaration and the Nuremberg Code, international human rights norms that lay out the need for informed consent in human subjects research. He and others saw how a healthy majority in Icelandic society may be under-valuing the need for privacy and control of medical information because they lacked their own sensitive medical histories of sickness and/or mental illness: it was these sensitive members of society that constitutional rules of privacy and autonomy were meant to protect vis-à-vis majoritarian decision-making. Although some individual doctors broke rank to support the Bill, the leaders of the Icelandic Medical Association agreed with Mannvernd, giving the opposition a boost from a highly respected national professional association. But, deCODE was simply able to build a larger network of supporters in Parliament and Icelandic society than Mannvernd, largely because of its demonstrated ability to raise investment capital, and the power of its economic promises.
But not only so. DeCODE’s successful appropriation of cultural tropes and resources reimagined Iceland, while constructing a future for it. In political debates and interviews, Stefansson could invoke the historic struggles of the Icelandic people with a brutal physical environment, and give these common histories new meaning and new value. These same hardships now made the Icelandic genome a valuable commodity in the global economy. What might seem to outsiders as a peculiar practice, the tracing of genealogical connections through countless generations, now became a lynch-pin of a cutting-edge biomedical technology. A common set of Icelandic founders had passed their genetic markers down through the generations, producing a key element in a new collective history of Iceland. But just as importantly, the database’s narrative of aggregation and social linkage provided a powerful cultural symbol of an integrated, independent, and modern people.
4 The Death of the Health Sector Database
In light of the development of our business since the Agreement was entered into, the lack of the required agreement with the [National University Hospital] and the fact that the Icelandic Data Protection Authority has not issued the required security certification, we do not expect to operate the IHD [i.e., the combined database] under the terms of the Agreement.21